Large numbers of cancers are linked to inheritance of susceptibility genes, especially for DNA repair. For example, alterations in OGG1 and MYH genes are associated with elevated risk of colorectal, lung, kidney and bladder cancer. Likewise, Ogg1/Myh deficient mice are prone to tumors. OGG1 and MYH genes are involved in the repair of oxidative DNA damage. Oxidative DNA damage can result in deleterious rearrangements in our genome leading to cancer. Therefore, antioxidants may reduce the level of oxidative DNA damage and rearrangements, hence prevent cancer. Pomegranate contains very high levels of antioxidants compared to other fruits and vegetables and may help reduce cancer risk. The goal of this pre-clinical pilot study is to understand whether pomegranate intake can reduce the level of genome rearrangements. Ogg1/Myh deficient mice will be treated with pomegranate extract (PomX) in their drinking water and genome rearrangements, including point mutations and deletions, will be determined in PomX treated mice and control mice receiving normal drinking water. If PomX reduces genome rearrangements, it will suggest that PomX may act as a cancer preventive agent. This pilot study would provide a justification to examine the long-term chemopreventive effect of PomX. These studies are significant to the mission of the National Institute of Health, because they will (i) advance our understanding of gene-nutrient interactions in the modulation of cancer risk, (ii) investigate the mechanisms of action of dietary antioxidants, and (iii) test a new strategy to prevent cancer in persons at increased genetic risk. This research could be transferred to the clinical setting for prevention of primary and recurrent cancers, especially in OGG1 and MYH mutation carriers. In addition, intake of pomegranate products could be recommended to help reduce cancer throughout the population.